Calcium/calmodulin-dependent protein kinase IV promotes imiquimod-induced psoriatic inflammation via macrophages and keratinocytes in mice

Yu, Yafen; Li, Bao; Ge, Huiyao; Zhen, Qi; Mao, Yan; Yu, Yan; Cao, Lu; Zhang, Ruixue; Li, Zhuo; Wang, Yirui; Fan, Wencheng; Zhang, Chang; Wang, Daiyue; Luo, Sihan; Bai, Yuanming; Chen, Shirui; Chen, Weiwei; Liu, Miao; Shen, Jijia; Sun, Liangdan

doi:10.1038/s41467-022-31935-8

Cited by 39 publications

(19 citation statements)

References 68 publications

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“…KN-93 is a CaMK4 inhibitor ( 43 - 45 ), but KN-93 also inhibits CaMKII. Liang et al reported that cyclic mechanical stress promotes chondrocyte proliferation and matrix synthesis via the integrin β1-CaMKII-Pyk2-ERK1/2 signaling cascade, but inhibition of CaMKII prevents cyclic mechanical stress-induced chondrocyte proliferation and matrix synthesis ( 46 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of CaMK4 as a sex-difference-related gene in knee osteoarthritis

Feng¹,

Zhang²,

Li³

et al. 2023

Ann Transl Med

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Background: Osteoarthritis (OA) is a common degenerative joint disease with a higher prevalence in females than in males. Sex may be a key factor affecting the progression of OA. This study aimed to investigate critical sex-difference-related genes in patients with OA and confirm their potential roles in OA regulation.Methods: OA datasets GSE12021, GSE55457, and GSE36700 were downloaded from the Gene Expression Omnibus database to screen OA-causing genes that are differentially expressed in the two sexes.Cytoscape was used to construct a protein-protein interaction network and determine hub genes. Synovial tissues of patients (male and female) with OA and female non-OA healthy controls were obtained to confirm the expression of hub genes and screen the key genes among them. Destabilization of the medial meniscus (DMM)-induced OA mice model was established to verify the screened key genes. Hematoxylin and eosin (HE) staining and Safranin O-fast green dye staining were employed to observe synovial inflammation and pathological cartilage status.Results: The abovementioned three datasets were intersected to obtain 99 overlapping differentially expressed genes, of which 77 were upregulated and 22 were downregulated in female patients with OA.The hub genes screened were EGF, AQP4, CDC42, NTRK3, ERBB2, STAT1, and CaMK4. Among them, Ca 2+ /calmodulin-dependent protein kinase-4 (CaMK4) was identified as a key sex-related gene for OA. It was significantly higher in female OA patients than in the cases of male patients. Moreover, CaMK4 was significantly increased in female patients with OA compared with the female non-OA group. These results suggest that CaMK4 plays an important role in the progression of OA. OA mouse models demonstrated that CaMK4 expression in the mice knee joint synovial tissue elevated after DMM, with aggravated synovial inflammation and significant cartilage damage. Cartilage damage improved after intraperitoneal administration of the CaMK4 inhibitor KN-93.Conclusions: CaMK4 is a key sex-related gene influencing the progression and pathogenesis of OA and may be considered as a new target for OA treatment.

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Section: Discussionmentioning

confidence: 99%

Identification of CaMK4 as a sex-difference-related gene in knee osteoarthritis

Feng¹,

Zhang²,

Li³

et al. 2023

Ann Transl Med

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“…Total RNA was harvested and isolated from the stable STRIP2 knockdown and scramble control cells. The total RNA was then performed to ribosomal RNA depleted RNA sequencing (RNA-Seq) protocols as previously described [29,30] . The library was sequenced on an Illumina Novaseq 6000.…”

Section: Methodsmentioning

confidence: 99%

STRIP2 motivates non-small cell lung cancer progression by modulating the TMBIM6 stability through IGF2BP3 dependent

Zhang

Chen

et al. 2022

Preprint

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Background: Striatin interacting protein 2 (STRIP2) is a core component of the striatin-interacting phosphatase and kinase (STRIPAK) complexes, which is involved in tumor initiation and progression via the regulation of cell contractile and metastasis. However, the underlying molecular mechanisms of STRIP2 in non-small cell lung cancer (NSCLC) progression remain largely unknown. Methods: The expressions of STRIP2 and IGF2BP3 in human NSCLC specimens and NSCLC cell lines were detected using quantitative RT-PCR, western blotting, and immunohistochemistry (IHC) analyses. The roles and molecular mechanisms of STRIP2 in promoting NSCLC progression were investigated in vitro and in vivo. Results: Here, we found that STRIP2 expression was significantly elevated in NSCLC tissues and high STRIP2 expression was associated with a poor prognosis. Knockdown of STRIP2 suppressed tumor growth and metastasis in vitroand in vivo, while STRIP2 overexpression obtained the opposite effect. Mechanistically, P300/CBP-mediated H3K27 acetylation activation in the promoter of STRIP2 induced STRIP2 transcription, which interacted with insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) and upregulated IGF2BP3 transcription. In addition, STRIP2-IGF2BP3 axis stimulated m6A modification of TMBIM6 mRNA and enhanced TMBIM6 mRNA stability. Consequently, TMBIM6 involved NSCLC cell proliferation, migration and invasion dependent on STRIP2 and IGF2BP3. In NSCLC patients, high co-expression of STRIP2, IGF2BP3 and TMBIM6 was associated with poor outcomes. Conclusions: Our findings indicate that STRIP2 interacts with IGF2BP3 to regulate TMBIM6 mRNA stability in an m6A-dependent manner and may represent a potential prognostic biomarker and therapeutic target for NSCLC.

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“…Total RNA was harvested and isolated from the stable STRIP2 knockdown and scramble control cells. The total RNA was then performed to ribosomal RNA depleted RNA sequencing (RNA-Seq) protocols as previously described [30,31]. The library was sequenced on an Illumina Novaseq 6000.…”

Section: Rna Sequencingmentioning

confidence: 99%

STRIP2 motivates non-small cell lung cancer progression by modulating the TMBIM6 stability through IGF2BP3 dependent

Zhang

Chen

et al. 2023

J Exp Clin Cancer Res

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Background Striatin interacting protein 2 (STRIP2) is a core component of the striatin-interacting phosphatase and kinase (STRIPAK) complexes, which is involved in tumor initiation and progression via the regulation of cell contractile and metastasis. However, the underlying molecular mechanisms of STRIP2 in non-small cell lung cancer (NSCLC) progression remain largely unknown. Methods The expressions of STRIP2 and IGF2BP3 in human NSCLC specimens and NSCLC cell lines were detected using quantitative RT-PCR, western blotting, and immunohistochemistry (IHC) analyses. The roles and molecular mechanisms of STRIP2 in promoting NSCLC progression were investigated in vitro and in vivo. Results Here, we found that STRIP2 expression was significantly elevated in NSCLC tissues and high STRIP2 expression was associated with a poor prognosis. Knockdown of STRIP2 suppressed tumor growth and metastasis in vitro and in vivo, while STRIP2 overexpression obtained the opposite effect. Mechanistically, P300/CBP-mediated H3K27 acetylation activation in the promoter of STRIP2 induced STRIP2 transcription, which interacted with insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) and upregulated IGF2BP3 transcription. In addition, STRIP2-IGF2BP3 axis stimulated m6A modification of TMBIM6 mRNA and enhanced TMBIM6 stability. Consequently, TMBIM6 involved NSCLC cell proliferation, migration and invasion dependent on STRIP2 and IGF2BP3. In NSCLC patients, high co-expression of STRIP2, IGF2BP3 and TMBIM6 was associated with poor outcomes. Conclusions Our findings indicate that STRIP2 interacts with IGF2BP3 to regulate TMBIM6 mRNA stability in an m6A-dependent manner and may represent a potential prognostic biomarker and therapeutic target for NSCLC.

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Calcium/calmodulin-dependent protein kinase IV promotes imiquimod-induced psoriatic inflammation via macrophages and keratinocytes in mice

Cited by 39 publications

References 68 publications

Identification of CaMK4 as a sex-difference-related gene in knee osteoarthritis

Identification of CaMK4 as a sex-difference-related gene in knee osteoarthritis

STRIP2 motivates non-small cell lung cancer progression by modulating the TMBIM6 stability through IGF2BP3 dependent

STRIP2 motivates non-small cell lung cancer progression by modulating the TMBIM6 stability through IGF2BP3 dependent

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